Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum
The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.INTRODUCTIONThe availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is...
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| creator | Trelle, Alexandra N Young, Christina B Vossler, Hillary Ramos Benitez, Javier Cody, Karly A Mendiola, Justin H Swarovski, Michelle S Guen, Yann Le Feinstein, Igor Butler, Robert R Channappa, Divya Romero, America Park, Jennifer Shahid-Besanti, Marian Corso, Nicole K Chau, Kelly Smith, Amanda N Skylar-Scott, Irina Yutsis, Maya V Fredericks, Carolyn A Tian, Lu Younes, Kyan Kerchner, Geoffrey A Deutsch, Gayle K Davidzon, Guido A Sha, Sharon J Henderson, Victor W Longo, Frank M Greicius, Michael D Wyss-Coray, Tony Andreasson, Katrin I Poston, Kathleen L Wagner, Anthony D Mormino, Elizabeth C Wilson, Edward N |
| description | The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.INTRODUCTIONThe availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.METHODSWe evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.RESULTSPlasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.DISCUSSIONLumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid posit |
| doi_str_mv | 10.1002/alz.14442 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_3148500033</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3148500033</sourcerecordid><originalsourceid>FETCH-LOGICAL-p153t-c174d719359e87facf992cd16b10cd33a5632cdcbbc165a467ff4ad9f48a3e2b3</originalsourceid><addsrcrecordid>eNpNjEtOwzAURSMEEuUzYAdvBpO2dmw3ybCq-EmVYADj6sV-oQbng1-C1O6DjbAQ1kRRGTC5957BPUlyIcVECpFOMWwnUmudHiQjaUw6NmlWHP7bx8kJ86sQWuTSjJLPx4BcI8y_v3Q6_U0BnoGpYd_7D4K-BcIYNmApUhkxANab0HoHaO1QDwF73zaAjYMukvO2Z4ie36CtwLYvzd7iyAbf0O4TW2bo1wTzsF2TryleMjjPhEzAHdk-DvVZclRhYDr_69Pk-eb6aXE3Xj7c3i_my3EnjerHVmbaZbJQpqA8q9BWRZFaJ2elFNYphWamdmzL0sqZQT3LqkqjKyqdo6K0VKfJ1d7bxfZ9IO5XtWdLIWBD7cArJXVuhBBKqR-BoG2D</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3148500033</pqid></control><display><type>article</type><title>Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum</title><source>Wiley Online Library Open Access</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Trelle, Alexandra N ; Young, Christina B ; Vossler, Hillary ; Ramos Benitez, Javier ; Cody, Karly A ; Mendiola, Justin H ; Swarovski, Michelle S ; Guen, Yann Le ; Feinstein, Igor ; Butler, Robert R ; Channappa, Divya ; Romero, America ; Park, Jennifer ; Shahid-Besanti, Marian ; Corso, Nicole K ; Chau, Kelly ; Smith, Amanda N ; Skylar-Scott, Irina ; Yutsis, Maya V ; Fredericks, Carolyn A ; Tian, Lu ; Younes, Kyan ; Kerchner, Geoffrey A ; Deutsch, Gayle K ; Davidzon, Guido A ; Sha, Sharon J ; Henderson, Victor W ; Longo, Frank M ; Greicius, Michael D ; Wyss-Coray, Tony ; Andreasson, Katrin I ; Poston, Kathleen L ; Wagner, Anthony D ; Mormino, Elizabeth C ; Wilson, Edward N</creator><creatorcontrib>Trelle, Alexandra N ; Young, Christina B ; Vossler, Hillary ; Ramos Benitez, Javier ; Cody, Karly A ; Mendiola, Justin H ; Swarovski, Michelle S ; Guen, Yann Le ; Feinstein, Igor ; Butler, Robert R ; Channappa, Divya ; Romero, America ; Park, Jennifer ; Shahid-Besanti, Marian ; Corso, Nicole K ; Chau, Kelly ; Smith, Amanda N ; Skylar-Scott, Irina ; Yutsis, Maya V ; Fredericks, Carolyn A ; Tian, Lu ; Younes, Kyan ; Kerchner, Geoffrey A ; Deutsch, Gayle K ; Davidzon, Guido A ; Sha, Sharon J ; Henderson, Victor W ; Longo, Frank M ; Greicius, Michael D ; Wyss-Coray, Tony ; Andreasson, Katrin I ; Poston, Kathleen L ; Wagner, Anthony D ; Mormino, Elizabeth C ; Wilson, Edward N</creatorcontrib><description>The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.INTRODUCTIONThe availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.METHODSWe evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.RESULTSPlasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.DISCUSSIONLumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.HIGHLIGHTSLumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.</description><identifier>ISSN: 1552-5279</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.14442</identifier><language>eng</language><ispartof>Alzheimer's & dementia, 2024-12</ispartof><rights>2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Trelle, Alexandra N</creatorcontrib><creatorcontrib>Young, Christina B</creatorcontrib><creatorcontrib>Vossler, Hillary</creatorcontrib><creatorcontrib>Ramos Benitez, Javier</creatorcontrib><creatorcontrib>Cody, Karly A</creatorcontrib><creatorcontrib>Mendiola, Justin H</creatorcontrib><creatorcontrib>Swarovski, Michelle S</creatorcontrib><creatorcontrib>Guen, Yann Le</creatorcontrib><creatorcontrib>Feinstein, Igor</creatorcontrib><creatorcontrib>Butler, Robert R</creatorcontrib><creatorcontrib>Channappa, Divya</creatorcontrib><creatorcontrib>Romero, America</creatorcontrib><creatorcontrib>Park, Jennifer</creatorcontrib><creatorcontrib>Shahid-Besanti, Marian</creatorcontrib><creatorcontrib>Corso, Nicole K</creatorcontrib><creatorcontrib>Chau, Kelly</creatorcontrib><creatorcontrib>Smith, Amanda N</creatorcontrib><creatorcontrib>Skylar-Scott, Irina</creatorcontrib><creatorcontrib>Yutsis, Maya V</creatorcontrib><creatorcontrib>Fredericks, Carolyn A</creatorcontrib><creatorcontrib>Tian, Lu</creatorcontrib><creatorcontrib>Younes, Kyan</creatorcontrib><creatorcontrib>Kerchner, Geoffrey A</creatorcontrib><creatorcontrib>Deutsch, Gayle K</creatorcontrib><creatorcontrib>Davidzon, Guido A</creatorcontrib><creatorcontrib>Sha, Sharon J</creatorcontrib><creatorcontrib>Henderson, Victor W</creatorcontrib><creatorcontrib>Longo, Frank M</creatorcontrib><creatorcontrib>Greicius, Michael D</creatorcontrib><creatorcontrib>Wyss-Coray, Tony</creatorcontrib><creatorcontrib>Andreasson, Katrin I</creatorcontrib><creatorcontrib>Poston, Kathleen L</creatorcontrib><creatorcontrib>Wagner, Anthony D</creatorcontrib><creatorcontrib>Mormino, Elizabeth C</creatorcontrib><creatorcontrib>Wilson, Edward N</creatorcontrib><title>Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum</title><title>Alzheimer's & dementia</title><description>The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.INTRODUCTIONThe availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.METHODSWe evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.RESULTSPlasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.DISCUSSIONLumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.HIGHLIGHTSLumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.</description><issn>1552-5279</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpNjEtOwzAURSMEEuUzYAdvBpO2dmw3ybCq-EmVYADj6sV-oQbng1-C1O6DjbAQ1kRRGTC5957BPUlyIcVECpFOMWwnUmudHiQjaUw6NmlWHP7bx8kJ86sQWuTSjJLPx4BcI8y_v3Q6_U0BnoGpYd_7D4K-BcIYNmApUhkxANab0HoHaO1QDwF73zaAjYMukvO2Z4ie36CtwLYvzd7iyAbf0O4TW2bo1wTzsF2TryleMjjPhEzAHdk-DvVZclRhYDr_69Pk-eb6aXE3Xj7c3i_my3EnjerHVmbaZbJQpqA8q9BWRZFaJ2elFNYphWamdmzL0sqZQT3LqkqjKyqdo6K0VKfJ1d7bxfZ9IO5XtWdLIWBD7cArJXVuhBBKqR-BoG2D</recordid><startdate>20241223</startdate><enddate>20241223</enddate><creator>Trelle, Alexandra N</creator><creator>Young, Christina B</creator><creator>Vossler, Hillary</creator><creator>Ramos Benitez, Javier</creator><creator>Cody, Karly A</creator><creator>Mendiola, Justin H</creator><creator>Swarovski, Michelle S</creator><creator>Guen, Yann Le</creator><creator>Feinstein, Igor</creator><creator>Butler, Robert R</creator><creator>Channappa, Divya</creator><creator>Romero, America</creator><creator>Park, Jennifer</creator><creator>Shahid-Besanti, Marian</creator><creator>Corso, Nicole K</creator><creator>Chau, Kelly</creator><creator>Smith, Amanda N</creator><creator>Skylar-Scott, Irina</creator><creator>Yutsis, Maya V</creator><creator>Fredericks, Carolyn A</creator><creator>Tian, Lu</creator><creator>Younes, Kyan</creator><creator>Kerchner, Geoffrey A</creator><creator>Deutsch, Gayle K</creator><creator>Davidzon, Guido A</creator><creator>Sha, Sharon J</creator><creator>Henderson, Victor W</creator><creator>Longo, Frank M</creator><creator>Greicius, Michael D</creator><creator>Wyss-Coray, Tony</creator><creator>Andreasson, Katrin I</creator><creator>Poston, Kathleen L</creator><creator>Wagner, Anthony D</creator><creator>Mormino, Elizabeth C</creator><creator>Wilson, Edward N</creator><scope>7X8</scope></search><sort><creationdate>20241223</creationdate><title>Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum</title><author>Trelle, Alexandra N ; Young, Christina B ; Vossler, Hillary ; Ramos Benitez, Javier ; Cody, Karly A ; Mendiola, Justin H ; Swarovski, Michelle S ; Guen, Yann Le ; Feinstein, Igor ; Butler, Robert R ; Channappa, Divya ; Romero, America ; Park, Jennifer ; Shahid-Besanti, Marian ; Corso, Nicole K ; Chau, Kelly ; Smith, Amanda N ; Skylar-Scott, Irina ; Yutsis, Maya V ; Fredericks, Carolyn A ; Tian, Lu ; Younes, Kyan ; Kerchner, Geoffrey A ; Deutsch, Gayle K ; Davidzon, Guido A ; Sha, Sharon J ; Henderson, Victor W ; Longo, Frank M ; Greicius, Michael D ; Wyss-Coray, Tony ; Andreasson, Katrin I ; Poston, Kathleen L ; Wagner, Anthony D ; Mormino, Elizabeth C ; Wilson, Edward N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p153t-c174d719359e87facf992cd16b10cd33a5632cdcbbc165a467ff4ad9f48a3e2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trelle, Alexandra N</creatorcontrib><creatorcontrib>Young, Christina B</creatorcontrib><creatorcontrib>Vossler, Hillary</creatorcontrib><creatorcontrib>Ramos Benitez, Javier</creatorcontrib><creatorcontrib>Cody, Karly A</creatorcontrib><creatorcontrib>Mendiola, Justin H</creatorcontrib><creatorcontrib>Swarovski, Michelle S</creatorcontrib><creatorcontrib>Guen, Yann Le</creatorcontrib><creatorcontrib>Feinstein, Igor</creatorcontrib><creatorcontrib>Butler, Robert R</creatorcontrib><creatorcontrib>Channappa, Divya</creatorcontrib><creatorcontrib>Romero, America</creatorcontrib><creatorcontrib>Park, Jennifer</creatorcontrib><creatorcontrib>Shahid-Besanti, Marian</creatorcontrib><creatorcontrib>Corso, Nicole K</creatorcontrib><creatorcontrib>Chau, Kelly</creatorcontrib><creatorcontrib>Smith, Amanda N</creatorcontrib><creatorcontrib>Skylar-Scott, Irina</creatorcontrib><creatorcontrib>Yutsis, Maya V</creatorcontrib><creatorcontrib>Fredericks, Carolyn A</creatorcontrib><creatorcontrib>Tian, Lu</creatorcontrib><creatorcontrib>Younes, Kyan</creatorcontrib><creatorcontrib>Kerchner, Geoffrey A</creatorcontrib><creatorcontrib>Deutsch, Gayle K</creatorcontrib><creatorcontrib>Davidzon, Guido A</creatorcontrib><creatorcontrib>Sha, Sharon J</creatorcontrib><creatorcontrib>Henderson, Victor W</creatorcontrib><creatorcontrib>Longo, Frank M</creatorcontrib><creatorcontrib>Greicius, Michael D</creatorcontrib><creatorcontrib>Wyss-Coray, Tony</creatorcontrib><creatorcontrib>Andreasson, Katrin I</creatorcontrib><creatorcontrib>Poston, Kathleen L</creatorcontrib><creatorcontrib>Wagner, Anthony D</creatorcontrib><creatorcontrib>Mormino, Elizabeth C</creatorcontrib><creatorcontrib>Wilson, Edward N</creatorcontrib><collection>MEDLINE - Academic</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trelle, Alexandra N</au><au>Young, Christina B</au><au>Vossler, Hillary</au><au>Ramos Benitez, Javier</au><au>Cody, Karly A</au><au>Mendiola, Justin H</au><au>Swarovski, Michelle S</au><au>Guen, Yann Le</au><au>Feinstein, Igor</au><au>Butler, Robert R</au><au>Channappa, Divya</au><au>Romero, America</au><au>Park, Jennifer</au><au>Shahid-Besanti, Marian</au><au>Corso, Nicole K</au><au>Chau, Kelly</au><au>Smith, Amanda N</au><au>Skylar-Scott, Irina</au><au>Yutsis, Maya V</au><au>Fredericks, Carolyn A</au><au>Tian, Lu</au><au>Younes, Kyan</au><au>Kerchner, Geoffrey A</au><au>Deutsch, Gayle K</au><au>Davidzon, Guido A</au><au>Sha, Sharon J</au><au>Henderson, Victor W</au><au>Longo, Frank M</au><au>Greicius, Michael D</au><au>Wyss-Coray, Tony</au><au>Andreasson, Katrin I</au><au>Poston, Kathleen L</au><au>Wagner, Anthony D</au><au>Mormino, Elizabeth C</au><au>Wilson, Edward N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum</atitle><jtitle>Alzheimer's & dementia</jtitle><date>2024-12-23</date><risdate>2024</risdate><issn>1552-5279</issn><eissn>1552-5279</eissn><abstract>The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.INTRODUCTIONThe availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.METHODSWe evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.RESULTSPlasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.DISCUSSIONLumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.HIGHLIGHTSLumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.</abstract><doi>10.1002/alz.14442</doi><oa>free_for_read</oa></addata></record> |
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| title | Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum |
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